Tachyphylaxis is a phenomenon described as the loss of response to a medication that was previously effective at an established dose. In a case report letter to the editors, Stefanie Cavalcanti, MD, Olga A. Lopez, MD, Simon Kung, MD, Jennifer L. Vande Voort, MD, Kristin Somers, MD, Mark A. Frye, MD, and Balwinder Singh, MD, MS, from the department of psychiatry and psychology at the Mayo Clinic, in Rochester, Minnesota, discuss "A Case of Tachyphylaxis After Long-Term Intravenous Racemic Ketamine for Treatment-Resistant Depression" in the May/June 2024 issue of the Journal of Clinical Psychopharmacology.

In this podcast about the case report, two co-authors, Dr. Singh and Dr. Cavalcanti, discuss the compelling history of one 56-year-old woman with treatment-resistant recurrent major depressive disorder. Her depression, ongoing for 10 years, featured prominent symptoms of depressed mood, social isolation, low energy, decreased appetite, and anhedonia. Past medication trials included selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants, mood stabilizers, antipsychotics, benzodiazepines, and bitemporal electroconvulsive therapy with limited benefit. Ketamine, which is used increasingly for treatment-resistant depression (TRD), and other psychiatric disorders, was tried next. Sustained clinical response was observed for the first 2 years of intravenous ketamine treatment despite ongoing life stressors. In the following years, a gradual reduction of response to subsequent ketamine infusions was observed in the patient, who required more frequent infusions to obtain the same response.

The authors emphasize that "the extension of ketamine's antidepressant effect with an increased dosage remains uncertain. … Ketamine has an addiction potential; thus, it is important to be mindful that increasing the ketamine dosage to address ketamine tachyphylaxis may enhance the potential for undesired consequences. Urgent studies investigating strategies to prolong ketamine's efficacy in adults with TRD are required."